Section 1 summarizes the qualifications of the investigators and institution (WUMS) to actively participate intellectually and operationally in protocol development, implementation, analysis of data and dissemination of results related to studies to be conducted by this Network for the prevention of hypoglycemia in insulin-treated diabetic subjects. Section 2 will outline a specific proposal for consideration by the Network. The specific proposal presented herein is entitled "Bedtime p2-adrenergic agonist therapy to prevent hypoglycemia in children with type 1 diabetes". Our proposal is based on studies, including those from our own group and other investigators, related to hypoglycemia-associated autonomic failure (HAAF) and its related components (defective glucose counterregulation, hypoglycemia unawareness, exercise-related HAAF, sleep-related HAAF) and thier association with the risk of hypoglycemia, and our preliminary studies suggesting that the p2-adrenergic agonist, terbutaline, diminishes nocturnal hypoglycemia in insulin-treated type 1 diabetic subjects. Herein, we propose initial pilot studies to determine the best dosage of terbutaline for the safe prevention of nocturnal hypoglycemia and to explore the physiologic effects of terbutaline on nocturnal hypoglycemia, hypoglycemia counterregulation and sleep efficiency. We then propose to use the results of these pilot studies and the collaborations established through this Network to develop and implement a large, multicenter, randomized, double-blind, placebo-controlled clinical trial to determine whether bedtime terbutaline reduces hypoglycemia to a degree that enables improvement of overall glycemic control. We also propose exploratory studies of the risks of hypo- and hyperglycemia on cognitive function. Establishing optimal glycemic control at the level necessary to achieve and maintain reduction of long term microvascular, macrovascular and neuropathic complications of diabetes has been limited by the risk of hypoglycemia. Strategies to prevent hypoglycemia that would enable better overall glycemic control would represent an important advance in the management of insulin-requiring diabetes mellitus. This research Network will develop and evaluate strategies to prevent hypoglycemia and improve diabetes control. [unreadable] [unreadable] [unreadable]